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EC number: 435-580-8 | CAS number: 56553-60-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Acceptable, well documented publication of a study performed equivalent to OECD guideline with the decomposition product boric acid
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- The Developmental Toxicity of Boric Acid in Rabbits
- Author:
- Price, C.J. et al.
- Year:
- 1 996
- Bibliographic source:
- Fundam. Appl. Toxicol. 34,176-187
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 991
- Reference Type:
- publication
- Title:
- The developmental toxicity of boric acid in mice, rats and rabbits
- Author:
- Heindel, J.J. et al.
- Year:
- 1 994
- Bibliographic source:
- Environ Health Perspect 102(Suppl 7):107-112
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- not specified
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Boric acid
- EC Number:
- 233-139-2
- EC Name:
- Boric acid
- Cas Number:
- 10043-35-3
- Molecular formula:
- BH3O3
- IUPAC Name:
- Boric acid
- Details on test material:
- - Name of test material: Boric acid
- Analytical purity: > 99%
- Stability under test conditions: Stable at room temperature for at least 28 days
- Lot/batch No.: 872703
- Supplier: Fisher Scientific Co.
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton Research Products inc., Denver, PA, USA
- Age at study initiation: approx. 5 months
- Weight at study initiation: 2690 - 4380 g
- Housing: individually in stainless steel cages with mesh flooring
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow (No. 5322), Ralston Purina Co., St. Louis, MO, USA; ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8 - 26.1
- Humidity (%): 47 - 89
- Photoperiod (hrs dark / hrs light): 12 / 12 (females), 10 / 14 (males)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- distilled/deionized
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
dose volume was adjusted daily.
VEHICLE
- Amount of vehicle (if gavage): 5 mL/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Assays (UVNIS spectroaxtry) conducted prior to dosing indicated that all formulations were within a range of 94-106% of the theoretinl concentrationa Formulations were used within the period of demcostrued stability.
- Details on mating procedure:
- - Impregnation procedure: artificial insemination
- Any other deviations from standard protocol: The study was performed in two replicates with two consecutive breeding days within each replicate
and 34 days between replicates. - Duration of treatment / exposure:
- Treatment: on gestational days 6 - 19
Termination: at day 30 of gestation - Frequency of treatment:
- Once daily on the mornings, 7 d/weeks
- Duration of test:
- 30 days (gestation days 0 - 30)
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
62.5, 125 or 250 mg/kg bw
Basis:
actual ingested
Boric acid
- Remarks:
- Doses / Concentrations:
10.9, 21.8 and 43.5 mg/kg bw
Basis:
actual ingested
Element Boron
- No. of animals per sex per dose:
- 30
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on reults of preliminary toxicity study where nonpregnant female rabbits (2/group) were dosed with BA (0 or 275 mg/kg bw/day, po) using a dose volume of 5 mL/kg in distilled/deionized water.
Examinations
- Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6-19, 25 and 30
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, at 2-3 days intervals
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 30
- Organs examined: liver, kidneys,uterus - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - External examinations: Yes: All per litter, including cleft palate
- Soft tissue examinations: Yes: All per litter, including sex determination
- Skeletal examinations: Yes: All per litter
- Head examinations: Yes: Half per litter
Litter size, number of dead foetuses and foetal weight were assessed. - Statistics:
- The doe or litter was considered the experimental unit for all statistical analyses . General Linear Models (GLM) procedures were applied for the analyses of variance (ANOVA) of maternal and fetal parameters . Prior to GLM analysis, an arcsinesquare root transformation was performed on all litter-derived percentage data and Bartlett's test for homogeneity of variance was performed on all data to be analysed by ANOVA . GLM analysis determined the significance of dose-response relationships and the significance of dose effects, replicate effects, and dose X replicate interactions . When ANOVA revealed a significant (p < 0 .05) dose effect, Dunnett's multiple comparison test compared exposed groups to control groups. One-tailed tests were used for all pairwise comparisons except maternal body and organ weights and fetal body weight. Nominal scale measures were analyzed by x² test for independence and by a test for linear trend on proportions. When a x² test showed significant groupwise differences, a one-tailed Fisher's exact probability test was used for pairwise comparisons of control and BA groups.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
No treatment-related clinical signs of toxicity were observed during the study, except for vaginal bleeding noted in 2-11 does/day on gd 19-30 at the high dose; these does had no live fetuses on day 30. Vaginal bleeding was also observed in one female in the low-dose group and in one in the mid-dose group. Two maternal deaths occurred (one each at the low- and mid-dose), but were not treatment-related. Food intake was decreased relative to that of controls on treatment days 6-15 at the high dose, and was increased after treatment ceased on days 25-30 at the mid and high doses. Body weight on gd 9-30, weight gain on gd 6-19, gravid uterine weight, and number of corpora lutea per dam were each decreased in the high-dose group. After correction for gravid uterine weights, however, maternal body-weight gain was increased at both the mid-and high- doses. Treatment with boric acid did not affect absolute or relative liver weight. Relative, but not absolute kidney weight increased at the high dose; kidney histopathology was unremarkable.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- Boric acid
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 21.9 mg/kg bw/day (actual dose received)
- Based on:
- element
- Remarks:
- Boron
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- Boric acid
- Basis for effect level:
- other: developmental toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 21.9 mg/kg bw/day (actual dose received)
- Based on:
- element
- Remarks:
- Boron
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Developmental effects were noted in the high dose group which consisted of a high rate of prenatal mortality (90% of implants/litter were reabsorbed compared with 6% in controls). Also, the percentage of pregnant females with no live fetuses was greatly increased (73% compared with 0% in controls), whereas the number of live fetuses per litter on day 30 was significantly reduced (2.3/litter compared with 8.8/litter in controls). Malformed live fetuses per litter increased significantly at the high dose, primarily due to the incidence of fetuses with cardiovascular defects, the most prevalent of which was interventricular septal defect (8/14 at high dose compared with 1/159 in controls). The incidence of skeletal malformations was comparable among groups. Relative to controls, the percentage of fetuses with variations (all types combined) was not significantly increased in any treated group, but the percentage with cardiovascular variations was significantly increased from 11% in controls to 64% in the high-dose group. Fetal body weights per litter at the high dose were depressed relative to control, but the difference was not statistically significant; however, this could have been due to the small sample size in the high-dose group. No developmental effects were found in the low- and mid-dose groups.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 125 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on increased resorptions and CVS malformations in surviving fetuses at 250 mg/kg bw/day
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Maternal toxicity:
Boric acid (mg/kg bw/d) | |||||
0 | 62.5 | 125 | 250 | ||
No. pregnant at euthanization | 18 | 23 | 20 | 22 | |
No. of live litters | 18 | 23 | 20 | 6 | |
No. of live fetuses | 159 | 175 | 153 | 14 | |
Maternal weight change (g) | Treatment period (GD 6 to 19) | 93 ± 30* | 132 ± 40 | 97 ± 51 | -137 ± 42** |
Gestation period (GD 0 to 30) | 357 ± 69* | 493 ± 51 | 543 ± 63** | 226 ± 35 | |
Corrected gestation wt. gain | -205 ± 78* | -52 ± 63 | 40 ± 57** | 165 ± 40** | |
Gravid uterine wa (g)a | 562 ± 40* | 504 ± 26 | 502 ± 28 | 62 ± 18** | |
Maternal liver weight (% bw) | 2.56 ± 0.13 | 2.8 ± 0.09 | 2.78 ± 0.08 | 2.87 ± 0.09 | |
Maternal kidney weight (% bw) | 0.46 ± 0.02 | 0.46 ± 0.01 | 0.47 ± 0.01 | 0.51 ± 0.01** | |
Renal pathology | 0/18 | 2/23 | 0/20 | 1/22 | |
Relative food consumption (g/kg/day) | Pretreatment period (GD 0 to 6) |
48.1 ± 1.7 | 48.0 ± 1.8 | 48.9 ± 2.4 | 46.4 ± 1.5 |
Treatment period (GD 6 to 19) | 38.8 ± 1.7* | 40.0 ± 2.0 | 38.7 ± 2.3 | 26.6 ± 2.2** | |
Posttreament (GD 19-25) | 36.9 ± 2.5* | 37.0 ± 2.6 | 40.0 ± 3.1 | 44.9 ± 2.2 | |
Posttreament (GD 25-30) | 24.5 ± 3.0 | 30.9 ± 2.1 | 33.9 ± 1.9** | 41.9 ± 1.6** |
* p < 0.05, linear trend. .
** p < 0.05, Dunnett's teat.
Developmental effects:
Boric acid (mg/kg bw/d) | |||||
0 | 62.5 | 125 | 250 | ||
No. implantation sites per litter (a) | 9.5 ± 0.8 | 26.1 ± 3.8 | 8.3 ± 0.5 | 8.6 ± 0.7 | |
% Resorptions per litter (a) | 6.3 ± 2.4* | 5.9 ± 1.9 | 7.7 ± 2.1 | 89.9 ± 5.0** | |
% Litters with one or more resorptions | 39 | 39 | 45 | 95*** | |
% Litters with 100% resorptions | 0 | 0 | 0 | 73*** | |
No. live fetuses per litter (b) | 8.8 ± 0.8* | 7.6 ± 0.6 | 7.7 ± 0.5 | 2.3 ± 0.8** | |
Average fetal body wt (g) per litter (b) | 44.8 ± 1.5 | 46.5 ± 1.4 | 45.7 ± 1.2 | 41.1 ± 2.7 | |
All malformations | % Fetuses per litter (b) | 25.5 ± 5.8* | 26.1 ± 3.8 | 30.4 ± 6.3 | 80.6 ± 16.3** |
%Litters | 72 | 78 | 75 | 83 | |
External malformations | % Fetuses per litter (b) | 0.8 ± 0.8* | 1.4 ± 1.0 | 1.0 ± 1.0 | 11.1 v 8.2** |
%Litters | 6 | 9 | 5 | 33 | |
Skeletal malformations | % Fetuses per litter (b) | 19.9 ± 5.4 | 19.9 ± 4.0 | 24.3 ± 6.4 | 38.9 ± 20.0 |
%Litters | 61 | 65 | 55 | 50 | |
Visceral malformations | % Fetuses per litter (b) | 7.3 ± 1.9* | 5.9 ± 2.0 | 7.4 ± 2.0 | 80.6 ± 16.3** |
%Litters | 50 | 35 | 45 | 83 | |
Cardiovascular malformations | % Fetuses per litter (b) | 2.7 ± 1.6* | 3.1 ± 1.5 | 4.2 ± 1.3 | 72.2 ± 16.5** |
%Litters | 17* | 22 | 35 | 83*** | |
All variations | % Fetuses per litter (b) | 67.7 ± 7.2 | 54.8 ± 5.1 | 40.4 ± 5.2 | 86.1 ± 9.0 |
%Litters | 94 | 100 | 90 | 100 | |
Cardiovascular variations | % Fetuses per litter (b) | 10.6 ± 5.5* | 5.7 ± 1.8 | 7.2 ± 2.5 | 63.9 ± 17.4** |
%Litters | 44 | 35 | 35 | 83 |
a) Includes all dams pregnant at euthanization; litter size is number of implantation sites per dam; mean ± SEM.
b) Includes only dams with live fetuses; litter size is number of live fetuses per dam; mean ± SEM.
* p < 0.05, linear trend. .
** p < 0.05, Dunnett's teat.
*** p< 0.05, Fisher’s exact test.
Applicant's summary and conclusion
- Conclusions:
- Due to observed maternal and developmental effects at 125 mg/kg bw/d Boric acid, this dose corresponding to 21.8 mg/kg bw/d Boron was determined to be the NOAEL.
- Executive summary:
Developmental toxicity of Boric acid was evaluated in a GLP study performed equivalent to OECD guideline 414, where groups of 30 New Zealand White) rabbits were administered boric acid once daily by gavage at doses corresponding to 0, 10.9, 21.9 and 43.8 mg boron/kg bw/day during major organogenesis on GD 6-19. The rabbits exposed to 43.8 mg boron/kg bw/day on gestation day 6-19 revealed decreased food intake during treatment, relative but not absolute kidney weight increase and vaginal bleeding. At the highest dose, prenatal mortality was increased (90% resorption/litter versus 6% in controls). In this dose group the number of live fetuses available for evaluation where dramaticall decreased compared to live fetuses in the other groups. Additionally, the resorption rate was disproportionally high (95%) and an increased incidente of malformed live foetuses/litter was observed primarily due to cardiovascular effects. Based on these results, the NOAEL for maternal and developmental toxicity was 125 mg/kg bw/d boric acid corresponding to 21.8 mg/kg bw/d Boron, respectively.
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